Antibodi Monoklonal Anti-CD3 Sebagai Terapi Diabetes Mellitus Tipe 1: Sebuah Kajian Sistematis dan Meta-analisis
DOI:
https://doi.org/10.29303/jku.v10i3.580Keywords:
Anti-CD3, C-peptide, HbA1C, Insulin, Type 1 Diabetes MellitusAbstract
Introduction: Type 1 Diabetes Mellitus (T1DM) is a chronic autoimmune disease which marked by a persistent increase in blood glucose (hyperglycemia). T1DM is thought to be caused by an autoreactivity of T cell which mediates the apoptosis of insulin-producing cells in the pancreas. Those mechanism causes a life-long dependance on exogen insulin. Current immunotherapy strategy is inhibiting or deleting the lymphocyte subset and/or through the use of agents which will induce the tolerance by activating regulatory T cell such as the use of anti-CD3. Therapy using monoclonal antibody also has a continous effect as compared to immunosupressive agents that traditionally being used.
Methods: A systematic review was conducted based on PRISMA through PubMed, ScienceDirect, Directory of Open Access Journal, Wiley, Cochrane Library, Google Scholar, and Scopus, searching for randomized controlled trials which analyze anti-CD3’s effects on clinical outcomes of T1DM patients. Studies selected were then assessed for bias risk with CONSORT criteria. Random-effects meta-analysis was performed to estimate the pooled mean difference (MD) along with their 95% confidence intervals (CIs).
Results: The search yielded ten RCTs with a total of 1,458 subjects. Anti-CD3 intervention is proven to be effective in reducing insulin’s usage (MD -0,18 [95% CI: -0.22, -0.13],I2=59%, p<0,0001) and HbA1C (MD -0.71[95% CI: -1.18, -0.24], I2=78%, p=0.003) significantly. Furthermore, there is another clinical benefits, such as reducing the decrease of C-peptide response significantly.
Conclusion: To conclude, anti CD-3 showed promising results to be widely implemented as treatment for T1DM patients.
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J. Gaglia and S. Kissler, "Anti-CD3 antibody for the prevention of type 1 diabetes - a story of perseverance," Biochemistry, vol. 58, no. 40, October 2019.
K. Herold, W. Hagopian, J. A. Auger, E. Poumian-Ruiz, L. Taylor, D. Donaldson, S. Gitelman, D. M. Harlan, D. Xu, R. A. Zivin and J. A. Bluestone, "Anti CD-3 Monoclonal Antibody in New- Onset Type 1 Diabetes Mellitus," The New England Journal of Medicine, vol. 346, no. 22, 2002.
R. D. Riley, K. G. Moons , K. I. E. Snell, J. Ensor, L. Hooft, D. G. Altman, J. Hayden, G. S. Collins and t. P. A. Debray , "A guide to systematic review and meta-analysis of prognostic factor studies," BMJ, vol. 364, p. k4597, 2019.
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A. Janez, C. Guja , A. Mitrakou, N. Latic , T. Tankova , L. Czupryniak, A. G. Tabak, M. Prazny, E. Martinka and L. S. Duvnjak, "Insulin Therapy in Adults with Type 1 Diabetes Mellitus: a Narrative Review," Diabetes Therapy, vol. 11, no. 11, pp. 387-409, 2020.
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K. C. Herold, S. E. Gitelman, M. R. Ehlers, P. A. Gottlieb, C. J. Greenbaum, W. Hagopian, K. D. Boyle, L. Keyes-Elstein, S. Aggarwal, D. Phippard, P. H. Sayre, J. McNamara and J. A. Bluestone, "Teplizumab (Anti-CD3 mAb) Treatment Preserves C-Peptide Responses in Patients With New-Onset Type 1 Diabetes in a Randomized Controlled Trial," Diabetes Journal, vol. 62, pp. 3766-3774, 2013.
W. Hagopian , R. J. Ferry, N. Sherry , D. Carlin, E. Bonvini, S. Johnson, K. E. Stein , S. Koenig, A. G. Daifotis, K. C. Herold and J. Ludvigsson, "Teplizumab Preserves C-Peptide in Recent-Onset Type-1 Diabetes," Diabetes, vol. 62, pp. 3901-3908, 2013.
N. Sherry , W. Hagopian, J. Ludvigsson , S. M. Jain , J. Wahlen, R. Ferry, B. Bode, S. Aronoff, C. Holland , D. Carlin, R. Wilder , K. King, S. Pillemer, E. Bonvini , K. Stein, S. Koenig, K. C. Herold and A. Daifotis , "Teplizumab for treatment of type 1 diabetes (Protégé study): 1-year result from a randomised, placebo-controlled trial," Lancet , vol. 378, no. 11, pp. 487-497, 2013.
K. C. Herold, S. Gitelman, C. Greenbaum, J. Puck, W. Hagopian, P. Gottlieb, P. Sayre, P. Bianchine, E. Wong, V. Seyfert-Margolis, K. Bourcier and J. A. Bluestone, "Treatment of patients with new onset Type 1 diabetes with a single course of anti-CD3 mAb teplizumab preserves insulin production for up to 5 years," Clinical Immunology, vol. 132, no. 2, pp. 166-173, 2009.
S. Demeester, B. Keymeulen, L. Kaufman, A. V. Dalem, E. V. Balti, U. V. d. Velde, Patrick Goubert, K. Verhaeghen, H. M. Davidson, J. Wenzlau, I. Weets, D. Pipeleers and F. Gorus, "Preexisting Insulin Autoantibodies Predict Efficacy of Otelixizumab in Preserveing Residual B-cel Function in Recent-Onset Type 1," Diabetes Care, vol. 38, pp. 644-651, 2015.
S. L. Sherwani, H. A. Khan, A. Ekhzaimy, A. Masood and M. K. Sakharkar , "Significance of HbA1c Test in Diagnosis and Prognosis of Diabetic Patients," Biomarker Insights, vol. 11, pp. 95-104, 2016.
B. Mianowska , W. Fendler , A. Szadkowska, A. Baranowska , E. G. Agaciak , J. Sadon, H. Keenan and W. Mlynarski, "HbA1c levels in schoolchildren with type 1 diabetes are seasonally variable and dependent on weather conditions," Diabetologia, vol. 54, no. 4, pp. 749-756, 2011.
C. Florkowski, "HbA1c as a Diagnostic Test for Diabetes Mellitus – Reviewing the Evidence," The Clinical Biochemist Reviews, vol. 34, no. 2, pp. 75-83, 2013.
K. C. Herold, W. Hagopian, J. A. Auger, E. Poumian-Ruiz, L. Taylor, D. Donaldson, S. E. Gitelman, D. M. Harlan, D. Xu, R. A. Zivin and J. A. Bluestone, "Anti-CD3 Monoclonal Antibody in New-Onset Type 1 Diabetes Mellitus," The New England Journal of Medicine, vol. 346, no. 22, pp. 1692-1698, 2002.
K. C. Herold, S. E. Gitelman, M. Umesh, W. Hagopian, B. Bisikirska, D. Donaldson, K. Rother, B. Diamond, D. M. Harlan and J. A. Bluestone, "A Single Course of Anti-CD3 Monoclonal Antibody hOKT3gamma1(Ala-Ala) Results in Improvement in C-Peptide Responses and Clinical Parameters for at Least 2 Years after Onset of Type 1 Diabetes," Diabetes Journal, vol. 54, pp. 1763-1769, 2005.
K. C. Herold, B. N. Bundy, A. Long, J. A. Bluestone, L. A. DiMeglio and M. J. Dufort, "An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes," The New England Journal of Medicine , vol. 381, pp. 603-613, 2019.
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Published
2021-12-18
How to Cite
Wiguna, V. V., Haq, A. D., & Rahayu, L. A. D. (2021). Antibodi Monoklonal Anti-CD3 Sebagai Terapi Diabetes Mellitus Tipe 1: Sebuah Kajian Sistematis dan Meta-analisis . Jurnal Kedokteran, 10(3), 581–593. https://doi.org/10.29303/jku.v10i3.580
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